<it>echinus</it>, required for interommatidial cell sorting and cell death in the <it>Drosophila </it>pupal retina, encodes a protein with homology to ubiquitin-specific proteases

• Main Authors: Gorski Sharon M, Guo Ming, Freeman J Douglas, Bosdet Ian, Copeland Jeffrey M, Hay Bruce A
• Format: Article
• Language: English
• Published: BMC 2007-07-01
• Series: BMC Developmental Biology
• Online Access: http://www.biomedcentral.com/1471-213X/7/82

<p>Abstract</p> <p>Background</p> <p>Programmed cell death is used to remove excess cells between ommatidia in the <it>Drosophila </it>pupal retina. This death is required to establish the crystalline, hexagonal packing of ommatidia that characterizes the adult fly eye. In previously described <it>echinus </it>mutants, interommatidial cell sorting, which precedes cell death, occurred relatively normally. Interommatidial cell death was partially suppressed, resulting in adult eyes that contained excess pigment cells, and in which ommatidia were mildly disordered. These results have suggested that <it>echinus </it>functions in the pupal retina primarily to promote interommatidial cell death.</p> <p>Results</p> <p>We generated a number of new <it>echinu</it>s alleles, some likely null mutants. Analysis of these alleles provides evidence that <it>echinus </it>has roles in cell sorting as well as cell death. <it>echinus </it>encodes a protein with homology to ubiquitin-specific proteases. These proteins cleave ubiquitin-conjugated proteins at the ubiquitin C-terminus. The <it>echinus </it>locus encodes multiple splice forms, including two proteins that lack residues thought to be critical for deubiquitination activity. Surprisingly, ubiquitous expression in the eye of versions of Echinus that lack residues critical for ubiquitin specific protease activity, as well as a version predicted to be functional, rescue the <it>echinus </it>loss-of-function phenotype. Finally, genetic interactions were not detected between <it>echinus </it>loss and gain-of-function and a number of known apoptotic regulators. These include Notch, EGFR, the caspases Dronc, Drice, Dcp-1, Dream, the caspase activators, Rpr, Hid, and Grim, the caspase inhibitor DIAP1, and Lozenge or Klumpfuss.</p> <p>Conclusion</p> <p>The <it>echinus </it>locus encodes multiple splice forms of a protein with homology to ubiquitin-specific proteases, but protease activity is unlikely to be required for <it>echinus </it>function, at least when <it>echinus </it>is overexpressed. Characterization of likely <it>echinus </it>null alleles and genetic interactions suggests that <it>echinus </it>acts at a novel point(s) to regulate interommatidial cell sorting and/or cell death in the fly eye.</p>